The object of this proposal is to devise molecular approaches for the inactivation of the encephalitogenic T cells that mediate experimental allergic encephalomyelitis (EAE). It is generally accepted that EAT is a CD4+ T cell mediated disease in which the autoimmune response to myelin proteins results in myelin destruction and paralysis. It has been shown that B cells can serve as potent antigen presenting cells (APC) and that T cell expansion in lymph nodes is dependent upon antigen presentation by B cells. However, it has also been shown that resting B cells care poor APC and in fac, can induce tolerance. After adoptive transfer into SCID or normal hosts B cells were found to be long-lived an to revert to a resting state. Our laboratory has developed protocols for the rapid and efficient transfer of exogenous genes into primary lymphocytes without perturbing these cells, such that they are still capable of homing to proper lymphoid organs. We propose to utilize retroviral-mediated gene transfer to express the known encephalitogenic antigens MBP and PLP in mature, long-lived B cells. After adoptive transfer, genetically modified B cells, should induce specific unresponsiveness to the encephalitogenic determinants they express.